我们的网站为什么显示成这样？

可能因为您的浏览器不支持样式，您可以更新您的浏览器到最新版本，以获取对此功能的支持，访问下面的网站，获取关于浏览器的信息：

|本期目录/Table of Contents|

p75NTR对兔心肌梗死模型跨室壁瞬时外向钾电流异质性的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第5期
页码:
641-646
栏目:
基础研究
出版日期:
2010-06-22

文章信息/Info

Title:
Effect of neurotrophin p75 receptor activation on transmural repolarization dispersion of outward potassium current in rabbits with myocardial infarction
作者:
林琨1; 赵旭燕1; 文毅2; 兰云峰2; 刘谟焓2; 李泱2
解放军总医院：1.心内科，2.老年心血管病研究所，北京 100853
Author(s):
LIN Kun1;  ZHAO Xu-yan1;  WEN Yi2;  LAN Yun-feng2;  LIU Mo-han2;  LI Yang2
1.Department of Cardiology, 2.Institute of Geriatric Cardiology, PLA General Hospital, Beijing 100853, China
关键词:
p75NTR; 陈旧性心肌梗死; 瞬时外向钾电流; 跨室壁异质性
Keywords:
neurotrophin p75 receptor;  myocardial infarction;  transient outward potassium current;  transmural dispersion repolarization
分类号:
R331.38;R542.22
DOI:
-
文献标识码:
A
摘要:
目的: 通过干预神经营养因子p75受体(p75NTR)探讨心肌梗死(MI)后神经过度增生对心肌细胞Ito，f异质性的影响。方法： 选日本大耳兔40只随机分为陈旧性心梗(HMI)组、p75 NTR激活组、p75 NTR抑制组和假手术组，每组10只(n=10)。采用酶解法制备3层心室肌单细胞，利用全细胞膜片钳技术记录电流。结果： 在以+50 mV的去极化刺激时，HMI组的Ito，f峰电流密度有所下降，在以p75NTR受体激活后，3层心肌Ito，f峰电流密度的下降更为明显，与假手术组比差异显著（P<0.05或P<0.01），其中以中层心肌Ito，f峰电流密度的下降程度最大；而应用p75NTR抑制剂后，下降的程度降低，与假手术组比无明显差异。与对照组相比，中层心肌细胞的Ito，f电压依赖性失活曲线在p75NTR激活组及HMI组均向负移，p75NTR抑制组得以恢复。Ito，f通道关闭态的τ值在4组的3层心肌细胞间存在明显差异，即p75NTR激活组及HMI组失活较快，尤以p75NTR激活组为甚，p75NTR抑制组的关闭态失活与对照组接近。结论： p75NTR激活后，3层心肌Ito，f峰电流密度下降明显，尤其以中层细胞为甚，此可能是导致跨室壁复极离散度显著增加，最终引起心律失常发生的原因之一。
Abstract:
AIM: To elucidate the effect of neurotrophin p75 receptor (p75NTR) on the transmural repolarization dispersion of the transient outward potassium current (Ito,f) of three layers of left ventricular myocytes in rabbits with myocardial infarction (MI). METHODS: Forty Japanese rabbits were divided into four groups: 1) HMI group, 2) p75 NTR activation group, 3) p75 NTR inhibition group and 4) sham group. Cardiomyocytes were isolated with enzyme digestion and the currents were recorded by whole-cell patch-clamp technique. RESULTS: Compared with those in the sham group, the densities of Ito,f in the HMI group and p75NTR(+) group were significantly reduced (P<0.01, n=10), especially in midmyocytes. This difference was reduced by inhibitor of p75NTR. Current densities of Ito,f in p75NTR(-) group was similar to that in sham group. Compared with that in sham group, the steady-state inactivation curve of Ito,f in the midmyocytes shifted to the negative in p75NTR(+) and HMI groups, and no obvious changes were observed in p75NTR(-) group. Significant differences were observed in the time constant values of closed-state inactivation of Ito,f in three layers of myocytes among the four groups, and closed-state inactivation was faster in p75NTR(+) and HMI groups, especially in p75NTR(+) group. The time constant values of closed-state inactivation of Ito,f in p75NTR(-) group was similar to that in sham group. CONCLUSIONS: Activation of p75NTR(+) reduces the current densities of Ito,f of three layers of myocytes, especially those in midmyocytes, which may result in the increase of transmural repolarization dispersion and incidence of arrhythmia.

参考文献/References

［1］Caporali A, Pani E, Horrevoets AJ, et al. Neurotrophin p75 receptor (p75NTR) promotes endothelial cell apoptosis and inhibits angiogenesis: implications for diabetes-induced impaired neovascularization in ischemic limb muscles［J］.Circ Res, 2008, 103(2):e15-e26.

［2］刘念，牛惠燕,李泱,等. 家兔陈旧性心肌梗死心室肌细胞钾离子电流的变化［J］. 中国病理生理杂志, 2004, 20(12):2227-2231.

［3］Zhou S, Cao JM, Swissa M, et al. Low-affinity nerve growth factor receptor p75NTR immunoreactivity in the myocardium with sympathetic hyperinnervation［J］. J Cardiovasc Electrophysiol, 2004, 15(4):430-437.

［4］Schultz JH, Janzen C, Volk T, et al. Kv4.2 and KChIP2 transcription in individual cardiomyocytes from the rat left ventricular free wall［J］. J Mol Cell Cardiol, 2005, 39(2):269-275.

［5］Zheng MQ, Tang K, Zimmerman MC, et al. Role of gamma-glutamyl transpeptidase in redox regulation of K+ channel remodeling in postmyocardial infarction rat hearts［J］.Am J Physiol Cell Physiol, 2009, 297(2):C253-C262．

［6］Ren C, Wang F, Li G, et al. Nerve sprouting suppresses myocardial I(to) and I(K1) channels and increases severity to ventricular fibrillation in rat［J］. Auton Neurosci, 2008, 144(1-2):22-29.

［7］李泱,马杰,肖建民,等. 兔左室壁三层心肌细胞的分离及动作电位、钙和钾电流分布的异质性［J］. 生理学报, 2002, 54(5):369-374.

［8］Rossow CF, Dilly KW, Yuan C, et al. NFATc3-dependent loss of I(to) gradient across the left ventricular wall during chronic beta adrenergic stimulation［J］.Mol Cell Cardiol, 2009,46(2):249-256.

［9］Campbell SG, Flaim SN, Leem CH, et al. Mechanisms of transmurally varying myocyte electromechanics in an integrated computational model［J］.Philos Transact A Math Phys Eng Sci, 2008, 366(1879):3361-3380.

［10］Rossow CF, Dilly KW, Santana LF. Differential calcineurin/NFATc3 activity contributes to the Ito transmural gradient in the mouse heart［J］. Circ Res, 2006, 98(10):1306-1313.

［11］Zhou S, Chen LS, Miyauchi Y, et al. Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs［J］. Circ Res, 2004, 95(1):76-83.

［12］Liu YB, Wu CC, Lu LS, et al. Sympathetic nerve sprouting, electrical remodeling, and increased vulnerability to ventricular fibrillation in hypercholesterolemic rabbits［J］.Circ Res, 2003, 92(10):1062-1064.

［13］Swissa M, Zhou S, Gonzalez-Gomez I, et al. Long-term subthreshold electrical stimulation of the left stellate ganglion and a canine model of sudden cardiac death［J］. J Am Coll Cardiol, 2004, 43(5):858-864.

[14]Billman GE. Cardiac autonomic neural remodeling and susceptibility to sudden cardiac death: effect of endurance exercise training［J］. Am J Physiol Heart Circ Physio, 2009, 297(4):H1171-H1193.

[15]王瑾,杨波,王腾. 家兔急性心肌梗死后梗死周边区心交感神经受损的研究［J］. 中国心脏起搏与心电生理杂志, 2008, 22（6）：539-542.

[16]Zhou S, Jung BC, Tan AY, et al. Spontaneous stellate ganglion nerve activity and ventricular arrhythmia in a canine model of sudden death［J］. Heart Rhythm, 2008, 5(1):131-139.

[17]Humpert PM, Kopf S, Djuric Z, et al. Levels of three distinct p75 neurotrophin receptor forms found in human plasma are altered in type 2 diabetic patients［J］. Diabetologia, 2007, 50(7):1517-1522.

备注/Memo

备注/Memo:
收稿日期：2010-01-13.基金课题：国家自然科学基金项目资助（30770901） 通讯作者：李泱，研究员，主要从事心律失常及心脏电生理研究Email：liyangbsh@163.com 作者简介：林琨，主治医师，博士Email：lk0102008@163.com
更新日期/Last Update: 2010-06-22